Skip to main content
Log in

The Effects of Omega-3 Polyunsaturated Fatty Acids on TNF-α and IL-10 Secretion by Murine Peritoneal Cells In Vitro

  • Original Article
  • Published:
Lipids

Abstract

Omega-3 polyunsaturated fatty acids (PUFA) affect immune response, partly by affecting cytokine secretion. Omega-3 PUFA decrease tumor necrosis factor (TNF)-α secretion by RAW 264.7 macrophages but increase TNF-α secretion by primary elicited peritoneal macrophages in vitro. In this study, the effects of omega-3 and omega-6 PUFA on lipopolysaccharide induced TNF-α and interleukin (IL)-10 secretion by murine primary resident and elicited peritoneal macrophages and by RAW 264.7 macrophages, were examined in vitro using an enzyme-linked immunosorbent assay. In addition, the effects of dietary omega-3 PUFA on the number of cells secreting these cytokines were examined with enzyme-linked immunospot assay. All cell types secreted more TNF-α but similar amounts of IL-10 when incubated with the omega-3 PUFA, eicosapentaenoic acid or docosahexaenoic acid, compared with that when incubated with the omega-6 PUFA, linoleic acid or arachidonic acid. Dietary fish oil did not affect the number of TNF-α secreting resident peritoneal macrophages but decreased the number of macrophages secreting IL-10 ex vivo. These results show that dietary omega-3 PUFA and omega-3 PUFA added to cells in vitro increase TNF-α secretion by resident peritoneal macrophages, probably by a direct effect on the cells. In contrast, omega-3 PUFA did not affect IL-10 secretion by the cells but decreased the number of cells secreting IL-10 ex vivo, possibly by affecting cell recruitment, maturation or proliferation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Arrington JL, Chapkin RS, Switzer KC, Morris JS, McMurray DN (2001) Dietary n-3 polyunsaturated fatty acids modulate purified murine T-cell subset activation. Clin Exp Immunol 125:499–507

    Article  PubMed  CAS  Google Scholar 

  2. Babcock TA, Helton WS, Hong D, Espat NJ (2002) Omega-3 fatty acid lipid emulsion reduces LPS-stimulated macrophage TNF-alpha production. Surg Infect (Larchmt) Summer 3(2):145–149

    Article  Google Scholar 

  3. Babcock TA, Kurland A, Helton WS, Rahman A (2003) Inhibition of activator protein-1 transcription factor activation by [omega]-3 fatty acid modulation of mitogen-activated protein kinase signaling kinases. JPEN 27(3):176–180

    CAS  Google Scholar 

  4. Bhattacharya A, Sun D, Rahman M, Fernandes G (2007) Different ratios of eicosapentaenoic and docosahexaenoic omega-3 fatty acids in commercial fish oils differentially alter pro-inflammatory cytokines in peritoneal macrophages from C57BL/6 female mice. J Nutr Biochem 18:23–30

    Article  PubMed  CAS  Google Scholar 

  5. Blok WL, Vogels MT, Curfs HJ, Eling WM, Buurman WA, van der Meer MWM (1992) Dietary fish oil supplementation in experimental gram-negative infection and in cerebral malaria in mice. J Infect Dis 165:898–903

    PubMed  CAS  Google Scholar 

  6. Bonatto SJ, Folador A, Aikawa J, Yamazaki RK, Pizatto N, Oliveira HH, Vecchi R, Curi R, Calder PC, Fernandes LC (2004) Lifelong exposure to dietary fish oil alters macrophage responses in Walker 256 tumor-bearing rats. Cell Immunol 231:56–62

    Article  PubMed  CAS  Google Scholar 

  7. Calder PC (2006) n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83(Suppl):1505S–1519S

    PubMed  CAS  Google Scholar 

  8. Carrick JB, Schnellmann RG, Moore JN (1994) Dietary source of omega-3 fatty acids affects endotoxin-induced peritoneal macrophage tumor necrosis factor and eicosanoid synthesis. Shock 2:421–426

    Article  PubMed  CAS  Google Scholar 

  9. Cathcart ES, Mortensen RF, Leslie CA, Conte JM, Gonnerman WA (1987) A fish oil diet inhibits amyloid P component (AP) acute phase responses in arthritis susceptible mice. J Immunol 139:89–91

    PubMed  CAS  Google Scholar 

  10. Chang HR, Arsenijevic D, Pechere JC, Piguet PF, Mensi N, Girardier L, Dulloo AG (1992) Dietary supplementation with fish oil enhances in vivo synthesis of tumor necrosis factor. Immunol Lett 54:13–18

    Article  Google Scholar 

  11. Chu AJ, Walton MA, Prasad JK, Seto A (1999) Blockade by polyunsaturated n-3 fatty acids of endotoxin-induced monocytic tissue factor activation is mediated by the depressed receptor expression in THP-1 cells. Surg Res 87:217–224

    Article  CAS  Google Scholar 

  12. Fritsche KL, Johnston PV (1988) Rapid autoxidation of fish oil in diets without added antioxidants. J Nutr 118:425–426

    PubMed  CAS  Google Scholar 

  13. Fritsche KL, Byrge M, Feng C (1999) Dietary omega-3 polyunsaturated fatty acids from fish oil reduce interleukin-12 and interferon-gamma production in mice. Immunol Lett 65:167–173

    Article  PubMed  CAS  Google Scholar 

  14. Geusens P, Wouters C, Nijs J, Jiang Y, Dequeker J (1994) Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. A 12-month, double-blind, controlled study. Arthritis Rheum 37:824–829

    Article  PubMed  CAS  Google Scholar 

  15. Hardardottir I, Kinsella JE (1991) Tumor necrosis factor production by murine resident peritoneal macrophages is enhanced by dietary n-3 polyunsaturated fatty acids. Biochim Biophys Acta 1095:187–195

    Article  PubMed  CAS  Google Scholar 

  16. Hardardottir I, Kinsella JE (1992) Increasing the dietary (n-3) to (n-6) polyunsaturated fatty acid ratio increases tumor necrosis factor production by murine resident peritoneal macrophages without an effect on elicited peritoneal macrophages. J Nutr 122:1942–1951

    PubMed  CAS  Google Scholar 

  17. Hubbard NE, Lim D, Somers SD, Erickson KL (1993) Effects of in vitro exposure to arachidonic acid on TNF-alpha production by murine peritoneal macrophages. J Leukoc Biol 54:105–110

    PubMed  CAS  Google Scholar 

  18. Jolly CA, Jiang YH, Chapkin RS, McMurray DN (1997) Dietary (n-3) polyunsaturated fatty acids suppress murine lymphoproliferation, interleukin-2 secretion, and the formation of diacylglycerol and ceramide. J Nutr 127:37–43

    PubMed  CAS  Google Scholar 

  19. Jolly CA, McMurray DN, Chapkin RS (1998) Effect of dietary n-3 fatty acids on interleukin-2 and interleukin-2 receptor alpha expression in activated murine lymphocytes. Prostaglandins Leukot Essent Fatty Acids 58:289–293

    Article  PubMed  CAS  Google Scholar 

  20. Komatsu W, Ishihara K, Murata M, Saito H, Shinohara K (2003) Docosahexaenoic acid suppresses nitric oxide production and inducible nitric oxide synthase expression in interferon-γ plus lipopolysaccharide-stimulated murine macrophages by inhibiting the oxidative stress. Free Radic Biol Med 34(8):1006–1016

    Article  PubMed  CAS  Google Scholar 

  21. Kremer JM (1991) Clinical studies of omega-3 fatty acid supplementation in patients who have rheumatoid arthritis. Rheum Dis Clin North Am 17:391–402

    PubMed  CAS  Google Scholar 

  22. Lo CJ, Chiu KC, Fu M, Lo R, Helton S (1999) Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NF kappa B activity. J Surg Res 82:216–221

    Article  PubMed  CAS  Google Scholar 

  23. Lo CJ, Chiu KC, Fu M, Chu A, Helton S (2000) Fish oil modulates macrophage P44/P42 mitogen-activated protein kinase activity induced by lipopolysaccharide. JPEN 24(3):159–166

    CAS  Google Scholar 

  24. Lokesh BR, Sayers TJ, Kinsella JE (1990) IL-1 and tumor necrosis factor synthesis by mouse peritoneal macrophages is enhanced by dietary n-3 polyunsaturated fatty acids. Immunol Lett 23:281–286

    Article  PubMed  CAS  Google Scholar 

  25. Novak TE, Babcock TA, Jho DH, Helton WS, Espat NJ (2003) NF-kappa B inhibition by omega-3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription. Am J Physiol Lung Cell Mol Physiol 284:L84–L89

    PubMed  CAS  Google Scholar 

  26. Petursdottir DH, Hardardottir I (2007) Dietary fish oil increases the number of splenic macrophages secreting TNF-α and IL-10 but decreases the secretion of these cytokines by splenic T cells of mice. J Nutr 137:665–670

    PubMed  CAS  Google Scholar 

  27. Petursdottir DH, Olafsdottir I, Hardardottir I (2002) Dietary fish oil increases tumor necrosis factor secretion but decreases interleukin-10 secretion by murine peritoneal macrophages. J Nutr 132:3740–3743

    PubMed  CAS  Google Scholar 

  28. Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 23:1939–1951

    Google Scholar 

  29. Renier G, Skamene E, DeSanctis J, Radzioch D (1993) Dietary n-3 polyunsaturated fatty acids prevent the development of atherosclerotic lesions in mice. Modulation of macrophage secretory activities. Arterioscler Thromb Vasc Biol 13:1515–1524

    CAS  Google Scholar 

  30. Shi L, Kishore R, McMullen MR, Nagy LE (2002) Chronic ethanol increases lipopolysaccharide-stimulated Egr-1 expression in RAW 264.7 macrophages. J Biol Chem 277(17):14777–14785

    PubMed  CAS  Google Scholar 

  31. Somers SD, Erickson KL (1994) Alteration of tumor necrosis factor-alpha production by macrophages from mice fed diets high in eicosapentaenoic and docosahexaenoic fatty acids. Cell Immunol 153:287–297

    Article  PubMed  CAS  Google Scholar 

  32. Switzer KC, McMurray DN, Morris JS, Chapkin RS (2003) (n-3) Polyunsaturated fatty acids promote activation-induced cell death in murine T lymphocytes. J Nutr 133:496–503

    PubMed  CAS  Google Scholar 

  33. Tappia PS, Grimble RF (1994) Complex modulation of cytokine induction by endotoxin and tumour necrosis factor from peritoneal macrophages of rats by diets containing fats of different saturated, monounsaturated and polyunsaturated fatty acid composition. Clin Sci (Lond) 87:173–178

    CAS  Google Scholar 

  34. Tappia PS, Man WJ, Grimble RF (1995) Influence of unsaturated fatty acids on the production of tumour necrosis factor and interleukin-6 by rat peritoneal macrophages. Mol Cell Biochem 143:89–98

    Article  PubMed  CAS  Google Scholar 

  35. Turek JJ, Schoenlein IA, Bottoms GD (1991) The effect of dietary n-3 and n-6 fatty acids on tumor necrosis factor-alpha production and leucine aminopeptidase levels in rat peritoneal macrophages. Prostaglandins Leukot Essent Fatty Acids 43:141–149

    Article  PubMed  CAS  Google Scholar 

  36. Wallace FA, Miles EA, Calder PC (1999) The effect of dietary fat on cytokine production by murine macrophages in different activation states. Lipids 34(Suppl):S145

    Article  PubMed  CAS  Google Scholar 

  37. Watanabe S, Hayashi H, Onozaki K, Okuyama H (1991) Effect of dietary alpha-linolenate/linoleate balance on lipopolysaccharide-induced tumor necrosis factor production in mouse macrophages. Life Sci 48:2013–2020

    Article  PubMed  CAS  Google Scholar 

  38. Watanabe S, Onozaki K, Yamamoto S, Okuyama H (1993) Regulation by dietary essential fatty acid balance of tumor necrosis factor production in mouse macrophages. J Leukoc Biol 53:151–156

    PubMed  CAS  Google Scholar 

  39. Weldon SM, Mullen AC, Loscher CE, Hurley LA, Roche HM (2007) Docosahexaenoic acid induces an anti-inflammatory profile in lipopolysaccharide-stimulated human THP-1 macrophages more effectively than eicosapentaenoic acid. J Nutr Biochem 18:250–258

    Article  PubMed  CAS  Google Scholar 

  40. Yaqoob P, Calder P (1995) Effects of dietary lipid manipulation upon inflammatory mediator production by murine macrophages. Cell Immunol 163:120–128

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from the Icelandic Research Fund, Graduate Education Fund (IHS), and The University of Iceland Research Fund.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ingibjorg Hardardottir.

About this article

Cite this article

Skuladottir, I.H., Petursdottir, D.H. & Hardardottir, I. The Effects of Omega-3 Polyunsaturated Fatty Acids on TNF-α and IL-10 Secretion by Murine Peritoneal Cells In Vitro. Lipids 42, 699–706 (2007). https://doi.org/10.1007/s11745-007-3081-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-007-3081-1

Keywords

Navigation